Radiation hair loss cut by circadian timing

Cancer radiation therapy may benefit from mouse study

Hair loss is one of the most visible and distracting effects of cancer radiation therapy. That hair loss can possibly be reduced by giving radiation in the evening, a time in the circadian cycle when hair follicles are resting, according to a new study. Applications may extend to chemotherapy protocols, the study stated.

The study, performed in mice, demonstrated dramatic reductions in hair loss by delivering gamma radiation when follicular cells were least rapidly dividing. Radiation preferentially kills cells when they are undergoing mitosis, so rapidly dividing cancer cells are most vulnerable. However, normal cells that are rapidly dividing can also be killed, causing hair loss, nausea and other unpleasant side effects.

The study was published Monday in the Proceedings of the National Academy of Sciences. The team included Salk Institute researchers Christopher Vollmers, Amandine Chaix and Satchidananda Panda. Cheng-Ming Chuong of USC's Keck School of Medicine and Panda are co-senior authors, and Maksim V. Plikus, also of Keck, is first author.

"Similar circadian synchronization strategy can be exploited to minimize side effects of radiation in other highly proliferative tissues, most prominently gastrointestinal epithelium and bone marrow," the study stated. "This would, however, require gaining better understanding of the physiological mechanisms of cell cycle regulation by the circadian clock in these tissues."

Circadian cycles are deeply ingrained in the evolutionary history of multicellular life, not only mammals but birds, reptiles, fruit flies and many other creatures. Since much of the genetic architecture is highly conserved, it's plausible that the results in mice pertain to people. Compared with fruit flies, mice and men are brethren.

"While we don't yet know if human hair follows that same clock we found in mice hair, it is true that facial hair in men grows during the day, resulting in the proverbial 5 o'clock shadow," Panda said in a Salk press release. "There is no 5 a.m. shadow if you shave at night."

Hair loss from radiation varies dramatically in mice depending on time of day. Top shows extensive hair loss in a mouse given 500 rads when hair cells were most actively dividing, their mitotic peak. Bottom shows reduced hair loss in a mouse given the same amount of radiation when hair cells were at the lowest point in the circadian mitotic cycle.
— Salk Institute

Hair loss from radiation varies dramatically in mice depending on time of day. Top shows extensive hair loss in a mouse given 500 rads when hair cells were most actively dividing, their mitotic peak. Bottom shows reduced hair loss in a mouse given the same amount of radiation when hair cells were at the lowest point in the circadian mitotic cycle.
/ Salk Institute

"These findings parallel daily changes in sensitivity of epidermis to external UV genotoxicity and can have important implications for designing radiation therapy and possibly chemotherapy protocols," the study stated. "More immediately, radiation treatment can be administered during the mitotic depression phase to minimize hair loss side effect."

Complicating such strategies, the paper said, some cancers have aberrant circadian cycles that must be factored into treatment by cancer chronotherapy.

The circadian-related differences in hair loss varied with the radiation dose. Mice were given doses from 400 to 700 rads. One group was irradiated when hair cells were most actively dividing, a circadian time known as CT50. The other group was irradiated when hair cells were least actively dividing, CT58.

"Especially dramatic were differences after 500-rad irradiation dose," the study stated. "Although mice in the CT50 group were almost completely bald, mice in the CT58 group maintained most of their hair."

At doses of 600 rads and higher, both sets of mice experienced nearly total depiliation, which the study said was probably due to the prolonged effects of high levels of cytotoxic radiation.

Another view of the difference in hair loss in mice given 500 rads of gamma radiation. Top mouse received radiation when hair follicle cells were dividing at the peak daily rate. Bottom mouse was irradiated at the lowest daily rate.— Salk Institute

Another view of the difference in hair loss in mice given 500 rads of gamma radiation. Top mouse received radiation when hair follicle cells were dividing at the peak daily rate. Bottom mouse was irradiated at the lowest daily rate.
/ Salk Institute

To check whether circadian cycles were really responsible for the differences, the study also tested mutant mice whose circadian cycles had been disrupted. These mice experienced nearly total hair loss at 500 rads, regardless of the time of day they were irradiated.

The study was supported by grants from the National Institutes of Health, The Leona M. and Harry B. Helmsley Charitable Trust, the Dana Foundation, the Glenn Foundation for Medical Research and the Edward Mallinckrodt Jr. Foundation.